tbuckley/cabot-search huggingface dataset:
Financial stress and burden among caregivers of cancer survivors in the United States.
Authors: Nicholas Theodoropoulos, Hui Xie, Qian Wang, Yannan Li, Chi Wen
Journal: Journal of Clinical Oncology (2022)

12027 Background: United States caregivers perform annual services equating to nearly $500 billion, with three-quarters of family caregivers utilizing personal funds. Nearly a third of all caregivers of cancer survivors report using all or most of their savings to contribute to the cost of cancer care. Prior studies indicate the duration of caregiving is associated with an increase in caregiving burden. This study aims to further describe the financial stress and burden in relation to caregiving duration for people who provide care to cancer survivors. Methods: A retrospective cross-sectional study was conducted using the 2015 and 2020 National Alliance for Caregiving and American Association of Retired Persons survey data. Multivariable logistic regressions were used to examine differences in reporting financial stress between various racial/ethnic groups while adjusting for education, income, and employment. Results: A total of 2,998 caregivers were included, where 208 of them were caring for cancer patients. Caregivers of cancer patients who provided care &gt; 21 hours/week were statistically more likely to be less educated, lower income, single, and unemployed compared to those who provided &lt; 21 hours/week. Caregiving for &gt; 21 hours/week compared to &lt; 21 hours/week is associated with being more likely to report communicating with healthcare professionals about a recipient's care (87.7% vs. 75.9%; p = 0.038). It is borderline significant that caregivers who provided care for &gt; 21 hours/week were more likely to advocate for recipients (68.7% vs. 56.8%; p = 0.086) and monitor condition severity to adjust care needs (84.9% vs. 70.7%; p = 0.100). After controlling for confounders (education, income, and employment), Non-Hispanic Black (odds ratio (OR) = 1.30; 95% CI: 1.02-1.65), Hispanic (OR = 1.39; 95% CI: 1.02-1.89), and Asian (OR = 1.51; 95% CI: 1.02-2.24) cancer caregivers had increased odds of reporting increased financial stress compared to Non-Hispanic White caregivers. Conclusions: Longer duration of caregiving to cancer survivors is associated with a greater burden for caregivers. Financial stress disparities related to caregiving exist between racial/ethnic groups, with non-white caregivers being more likely to report increased financial strain. Special financial programs are needed to assist caregivers of cancer survivors, a growing but understudied population.
Impact of SF3B1 mutation on outcomes in myelofibrosis.
Authors: Prithviraj Bose, Jayastu Senapati, Lucia Masarova, Naveen Pemmaraju, Guillermo Montalban Bravo, Sherry Pierce, Lingsha Zhou, Guillermo Garcia-Manero, Hagop M. Kantarjian, Srdan Verstovsek
Journal: Journal of Clinical Oncology (2022)

e19080 Background: Splicing factor 3B subunit 1 ( SF3B1) mutations have been shown to confer a unique phenotype in MDS and MDS/MPN overlap syndromes, with ring sideroblasts, thrombocytosis and favorable prognosis. In myelofibrosis (MF) the frequency of SF3B1 mutation is &lt;10% and may play a less important role in disease outcomes (Lasho et. al, Leukemia, 2011). Methods: We retrospectively analyzed all patients (pts) with WHO-defined MF (primary, including pre-fibrotic MF, or progressed from PV or ET) seen at our center from Jan. 2017 through Jul. 2021. We compared disease phenotypes, MPN driver and co-occurring mutations, cytogenetics, dynamic IPSS (DIPSS) score, transfusion requirements, treatment characteristics and survival outcomes between patients with SF3B1-mutated ( SF3B1 + ) and -wild type ( SF3B1 - ) MF. Results: A total of 381 pts were identified, 29 (8%) of whom were SF3B1 + . There were similar frequencies of JAK2, CALR, MPL mutations and “triple negative” MF in the 2 groups (Table). The median number of SF3B1 mutations was 1 (range, 1-2); K666N being the most common (52%). The 2 groups were similar in regard to their baseline hemoglobin, white blood cell counts, platelets, co-occurring mutations, symptom burden and DIPSS but more SF3B1 + pts were PRBC transfusion-dependent at presentation than SF3B1 - pts (38% vs. 15%, p=0.003). At a median follow up of 17.2 months for the entire cohort (range, 0.1- 52.2 mos., 22.6 mos. for SF3B1 + and 16.8 mos. for SF3B1 - ), 41 pts had died [14% SF3B1 + and 10% SF3B1 - , p=0.5] and 7 pts (1 SF3B1 + and 6 SF3B1 - ) had leukemic transformation. The median estimated OS was 230 months for SF3B1 - vs. not reached for SF3B1 + pts (p = 0.6). Conclusions: SF3B1 mutation is an uncommon event in MF and does not substantially affect disease phenotype and outcomes. MF pts with SF3B1 mutation are more likely to be PRBC transfusion dependent.[Table: see text]
m6A modification regulates early human cardiomyocyte lineage specification
Authors: G Spano, F De Majo, JC Hegenbarth, M Tiburcy, WH Zimmermann, LJ De Windt
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 813716. Background RNA modifications affect gene expression through the regulation of RNA metabolism. N6-methyladenosine (m6A) is the most abundant post-transcriptional modification that occurs in RNAs. Its dynamic expression is regulated by the "writer complex" (methyltransferases) and "erasers" (demethylases) and affects numerous biological functions, including mammalian embryonic stem cell (ESC) fate specification. However, the role of m6A in human cardiomyocyte (CM) lineage specification remains unclear. Purpose In this study, we aim to investigate the impact of m6A modification on early human cardiomyocyte differentiation, following the dynamic expression of m6A modification of human induced pluripotent stem cells (hiPSC) into cardiomyocytes (hiPSC-CMs). Methods hiPSCs were differentiated into hiPSC-CMs by mesodermal induction, followed by inhibition of WNT-signaling. We collected hiPSC derivates at different stages of the differentiation protocol: hiPSCs, hiPSC-derived cardiac mesoderm cells, hiPSC-derived cardiomyocyte progenitors (hiPSC-CPCs), and mature hiPSC-CMs. Protein levels of m6A key regulators were analyzed. To systematically profile the expression of m6A modification, we subjected hiPSC derivates to m6A immunoprecipitation combined with deep sequencing (MeRIP-seq) and RNA-seq. Enrichment analyses of gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were conducted to elucidate the biological significance of differentially expressed and methylated genes. Results m6A distribution analysis on hiPSC derivates revealed a conserved pattern on a transcriptome-wide level: methylation sites are mainly located nearby the stop coding regions. However, we observed upregulated levels of writer proteins during the transition of hiPSC-derived cardiac mesoderm cells into hiPSC-CPCs. Interestingly, the dynamic changes in writer protein levels toward hiPSC-CPC transition were accompanied by a higher number of significantly upregulated and hyper-methylated mRNA transcripts. GO and KEGG analyses indicated hyper-methylated upregulated transcripts are enriched in muscle cell differentiation, cardiac physiology and calcium and MAPK signaling pathways regulating heart contraction. Conclusion For the first time, our study provides evidence that m6A modification is a mediator of early human cardiomyocyte differentiation. The role of specific writer regulators and individual m6A transcripts will be further investigated.
Predictive value of TGFβ1/TGFBR2 ratio for evaluating the effectiveness of treatment in patients with diffuse large B-cell lymphoma (DLBCL).
Authors: Valeria A. Bandovkina, Elena M. Frantsiyants, Luiza B. Kushtova, Yuliya Yu. Kozel, Aleksandr V. Snezhko, Viktoria V. Dmitrieva, Olga V. Kozyuk, Sergey A. Malinin, Lusegen Kh. Chalkhakhyan, Gennadiy V. Kaminskiy, Irina B. Lysenko, Nadezhda V. Nikolaeva, Oleg I. Kit
Journal: Journal of Clinical Oncology (2022)

e19559 Background: About 30-40% of patients with diffuse large B-cell lymphoma (DLBCL) do not respond to treatment, they subsequently relapse or remain refractory, so the search for predictive factors for the treatment effectiveness is relevant. TGF-β is a pleiotropic regulator of many pathophysiological processes, including carcinogenesis and immune responses, and its signals are initiated via its binding with proteins, including TGF-β receptor type 1 and type 2 (TGFBR2). The purpose of this study was to analyze the TGFβ1 and TGFBR2 blood levels and their ratio in patients with DLBCL depending on the treatment efficacy. Methods: The study included 63 patients (32 men and 31 women aged 23-88 years, median age 55.6 years) diagnosed with DLBCL. Blood levels of TGFβ1 and TGFBR2 were determined by ELISA before and after treatment. Stage I DLBCL was registered in 6 (9.5%) patients, stage II in 25 (39.7%), stage III in 5 (7.9%), stage IV in 27 (42.9%). All patients received standard treatment with R-CHOP, R-CHOEP, R-EPOCH. Direct results of the treatment were assessed by Cheson’s criteria. By their response to the therapy, patients were divided into 3 groups: group 1 (25.4%) – relapsed disease, group 2 (25.4%) – refractory disease, and group 3 (49.2%) – remission. A group of healthy donors included 20 men and women. All patients gave their informed consent to the study. Results: Blood levels of TGF-β1 in all patients before the treatment were higher than in donors by 2.1 times, and after the treatment by 2.4, 1.9 and 1.9 times, respectively, in groups 1, 2 and 3. The values between the groups did not differ significantly. Levels of TGFBR2, on the contrary, were lower in patients before treatment than in donors by 3 times, and after treatment by 3.5 in group 1, by 4 times in group 2, and similar to the norm in group 3. The TGFβ1/TGFBR2 ratios in patients before treatment were 6.1 times higher than the norm. After treatment, the ratio in patients of groups 1 and 2 were 8.6 and 7.2 times higher than in healthy donors. The ratio in patients of group 3 was 2.3 times higher than in healthy donors, and the value differed significantly from the values in groups 1 (3.8 times lower) and 2 (3.2 times lower). Conclusions: Monitoring the TGFβ1/TGFBR2 ratio in DLBCL patients before and during the treatment will allow promptly determination of adverse outcomes and changing the treatment regimen.
The future landscape of cancer incidence and mortality until 2036 in the Russian Federation.
Authors: Ilya Tsimafeyeu, Lola Rahib
Journal: Journal of Clinical Oncology (2022)

e22518 Background: Understanding the future of the burden of cancer is important to plan for future research funding, allocations of resources and other efforts. In 2019, the most incident solid tumors in Russia were colorectal, breast, lung, prostate, and gastric cancers; most deaths were lung, colorectal, gastric, breast, and pancreas cancers. We project cancer incidences and death to the year 2036 utilizing population growth estimates and observed current rates and trends in Russia. Methods: Average annual percent change (AAPC) adjusted estimations of cancer incidences and death to 2036 were calculated for the 10 most incident and deadly cancers for male and female individuals. We combined the most recent sex and cancer-specific delay-adjusted incidence rates from the Herzen Russian Cancer Statistics (official Russian cancer statistics) and GLOBOCAN database with existing Federal State Statistics Service (Rosstat) demographic population growth projections by sex to calculate estimated incidences and death to 2036. Calculations assume that the annual percent change in the incidence and death rates observed will remain constant through 2036. Results: We project that by 2036 the incidence will increase by 19.5% and the most incident cancers in Russia will be different than the current rankings. Excluding non-melanoma skin cancer, breast is projected to be the most incident cancer with 99,700 diagnoses (currently second most incident; 73,918 diagnoses in 2019), colorectal is projected to be second with 95,200 diagnoses (currently first, 77,062 diagnoses in 2019). Lung (60,113 diagnoses in 2019) and prostate (45,763 diagnosis in 2019) will drop from fourth and third place to third and fourth place with 85,400 and 53,100 diagnoses in 2036 respectively. Despite the increase in incidence, cancer deaths will decline by 18% by 2036. Lung and colorectal cancer are projected to continue to be the top 2 leading causes of cancer related death with 35,800 deaths in 2036 due to lung cancer and 32,100 deaths due to colorectal cancer. Pancreas cancer is projected to surpass breast and gastric cancer to become the 3 rd leading cause of cancer related deaths in 2036 (21,800 deaths in 2036). Breast cancer is projected to move from the fourth leading cause of cancer related deaths to fifth and gastric cancer will no longer be one of the top 5 causes of cancer deaths. Conclusions: We present projections on cancer incidence and deaths to 2036 in Russia. We show a shift in the rankings of the top 5 most common cancers and most markedly we show that pancreas cancer will be the third leading (currently fifth) cause of cancer related deaths by 2036. These projections can guide future research focus and planning.
Prospective, multicenter study on non-pharmacological, patient related predictive factors of chemotherapy induced nausea and vomiting (CINV): A NOGGO-EMRISK trial.
Authors: Jalid Sehouli, Gülten Oskay-Özcelik, Dario Zocholl, Anna-Sophia Klemt, Nikola Bangemann, Oliver Albrecht, Hans-Joachim Strittmatter, Pauline Wimberger, Anna Kaczerowsky, Ralf Lorenz, Wencke Ruhwedel, Tanja N. Fehm, Andreas Zahn, Oliver Tome, Miriam Markert, Dietrich Hager, Andreas Zorr, Maren Keller, Hannah Rittmeister, Jacek P. Grabowski
Journal: Journal of Clinical Oncology (2022)

e24107 Background: Despite many years of clinical research and development, nausea and vomiting remain challenging toxicities related to chemotherapy. The aim of our study was assessment of non-pharmacological, patient-related risk factors for chemotherapy-induced nausea and vomiting and development of unique predictive score in patients with gynaecological malignancies planned for chemotherapy. Methods: A research-based questionnaire of 27 risk factors was generated and provided to patients diagnosed with gynaecological malignancies prior to indicated chemotherapy. The data on nausea and vomiting from at least 3 cycles therapy was collected. Variable selection via stepwise and LASSO regression combined with patients history was used to identify a small set of questions with high predictive power. As risk prediction model, a Bayesian logistic regression was implemented with a cut-off chosen to yield a sensitivity of 80%. Area under the curve analysis (AUC) was conducted, and accuracy of prediction was calculated. Results: In total 191 patients were enrolled. The most frequent diagnosis and chemotherapy was ovarian cancer (69%) and carboplatinum/paclitaxel combination (57.7%), respectively. Six factors (emetogenic potential of the therapy, educational status, nausea and vomiting due to other medication, motion sickness, anxiety from therapy in general and anxiety from nausea due to therapy) were identified as most important predictive factors. All questions were answered by 132 (69.1%) patients. Among those 97 (68%) reported nausea or vomiting. The AUC of the predictive score consisting mentioned factors was 0.741, with a sensitivity of 80.4%, specificity of 51.4% and an overall accuracy of 72.7%. Conclusions: Patients related risk factors are missing in selection of the antiemetic prophylaxis in patients under chemotherapy. Presented predictive score showed very promising predictive power and is going to be validated in further phase of the trial. Clinical trial information: DRKS-ID: DRKS00015151.
Piflufolastat F 18-PET/CT in patients with prostate cancer: An analysis of OSPREY (cohorts A and B) standardized uptake value (SUV) results stratified by PSA and Gleason score.
Authors: Michael A. Gorin, Steven P. Rowe, Kenneth J. Pienta, Peter R. Carroll, Frederic Pouliot, Stephan Probst, Lawrence Saperstein, Mark Preston, Ajjai Shivaram Alva, Akash Patnaik, Nancy Stambler, Barry A. Siegel, Michael J. Morris
Journal: Journal of Clinical Oncology (2022)

5024 Background: The OSPREY clinical trial was a phase 2/3 prospective study of prostate specific membrane antigen (PSMA) PET/CT using piflufolastat F 18. Piflufolastat F 18 (aka 18 F-DCFPyL or PyL) is a novel PSMA-targeting radiopharmaceutical approved for imaging of PCa pts both at initial staging and for disease recurrence. Here we describe SUV results by biopsy status, baseline PSA levels, and Gleason score (GS). Methods: Piflufolastat F 18-PET/CT was evaluated in men with NCCN high-risk PCa scheduled to undergo radical prostatectomy with pelvic lymphadenectomy (RP-PLND) (Cohort A) and men with radiologically suspected recurrent/metastatic PCa (Cohort B). A single IV dose of 9 mCi (333 MBq) of piflufolastat F 18 was administered followed by PET/CT acquisition 1-2 hours later. Piflufolastat F 18 uptake in various lesion locations as defined by maximum and peak SUV (SUVmax, SUVpeak) were determined by three blinded, independent central readers for each tissue (e.g., bone, lymph nodes (LN), soft tissue). To measure SUVs, the reader placed a volume of interest (VOI) on each identified lesion. SUVmax was defined as the maximum single-voxel SUV within the VOI. SUVpeak within the VOI was defined as the average SUV within a fixed-sized VOI (1 cm diameter sphere), representing the cluster with the highest average SUV. Results: 345 men underwent piflufolastat F 18-PET/CT. Cohort B (n = 93evaluable) SUVmax and SUVpeak were significantly higher for biopsy positive (+)(one biopsy lesion/pt) when compared to biopsy negative (-) lesions from bone and LN. SUVpeak for biopsied bone and LN (Cohort B) appeared to increase with rising baseline PSA. In high-risk PCa pts, SUVpeak for prostate (Cohort A; n = 252 evaluable) increased with baseline PSA and were highest for GS 9-10 (Table). Conclusions: Piflufolastat F 18-PET/CT uptake was significantly higher in biopsy + lesions and increased with baseline PSA. Prostate SUVpeak was highest for GS 9-10. Clinical trial information: NCT02981368. [Table: see text]
Comparative efficacy and safety of immunotherapy for advanced NSCLC: A systematic review and network meta-analysis.
Authors: Bin Xu, Chen Zhao, Hao Zhong, Tianyu Lei, Huibo Zhang, Jie Wu, Lan Li, Yi Yao, Qibin Song
Journal: Journal of Clinical Oncology (2022)

e21028 Background: Advanced non-small cell lung cancer (NSCLC) patients responded differently to checkpoint inhibitors (ICIs) therapy, leading to the confuse of choosing the optimal regimens for patients. Therefore, we performed this network meta-analysis to compare different agents across clinical trials. Methods: We searched databases, including EMBASE, PubMed, ClinicalTrials and etc, for abstracts, full-text articles and minutes of the annual meetings published from database inception through Oct 01, 2021. Phase 3 randomized clinical trials (RCTs) of first-line immunotherapy or combinations for adcanced (stage III/IV or recurrent) NSCLC were included. We selected 26 trials evaluating different ICIs (Atezolizuma (atezo), Pembrolizumab (pem), Nivolumab(nivo), Durvalumab (durva), Camrelizumab (camre), Tislelizumab (tisle), Sintilimab (sint), Sugemalimab (suge), Toripalimab (tori), Cemiplimab (cemip)) and combinations based on them. Primary outcomes of interests were overall survival (OS) and progression-free survival (PFS). Secondary outcomes of interests were objective response rate (ORR), and adverse events (AEs). Hazard ratio (HRs) and 95% confidence intervals (CI) were used to represent the results of OS and PFS. The subgroup analysis (pathological type, PD-L1 expression, gender, smoking history, ECOG score, metastasis status and ethnicity) was performed and the treatments were ranked in it and overall population. Results: In our study, all ICIs-based regimens had benefit in OS and PFS compared with chemotherapy. The network meta-analysis for OS showed the combination of Camre-Chemo ranked 1st in overall population, and most of dual ICIs-based regimens, except Nivo-Ipi-Chemo, showed minor improvement in OS while possess more safety concerns compared with other regimens. Atezo-Beva-Chemo (ranked 1st in PFS, 20th in safety), has shown good efficacy but was revealed with lower safety. Sint-Chemo demonstrated promising efficacy in PFS, but it remains to be seen whether the effectiveness could be transformed into OS benefit due to the lack of related data. Pem-Chemo (ranked 1st in ORR) demonstrated the best response to tumors in all treatments regardless of PD-L1 expression. In subgroup analysis, for patients with poor health conditions (≥65 years or with ECOG = 1), multi-drug combination regimens, such as Nivo-Ipi-Chemo and Atezo-Beva-Chemo, showed better benefits in PFS and OS compared with only chemo but had no significant advantages than any other treatments. Conclusions: In our study, we provide relative comprehensive results for latest researches of first-line ICIs. Overall, Care-Chemo, Pem-Chemo, Sint-Chemo, are prior to be recommended according to our study.